Thesis (Ph. D.)--University of Nevada, Reno, 2006. / "August, 2006." Includes bibliographical references (leaves 214-226). Online version available on the World Wide Web.

Thesis (Ph. D.)--University of Hong Kong, 2007. / Also available online.

Thesis (Ph.D.)--Aberdeen University, 2009. / Title from web page (viewed on July 1, 2009). Includes bibliographical references.

No description available.

It is generally held that adenosine 3',5'-cyclic monophosphate (cAMP) mediates smooth muscle relaxation by the activation of cAMP-dependent protein kinase (PKA). This hypothesis was tested in two intact smooth muscle preparations, the rat vas deferens and the bovine coronary artery, using exogenously applied cAMP and cAMP analogs. After 30 minutes of incubation, N⁶,2'-0-dibutyryl-cAMP (dBu-cAMP) (1 - 100 μM) inhibited phenylephrine (PE)-induced tension generation in the rat vas deferens in a dose-dependent manner. This analog (10 μM) also activated the soluble fraction of PKA but did not activate the particulate fraction kinase. In contrast, 8-bromo-cAMP (8Br-cAMP) (10 -100 μM) did not have any significant effect on inhibition of PE-induced tension after 30 minutes of incubation but, at a concentration of 10 μM, significantly activated both the soluble and particulate fractions of PKA. The time course of activation of soluble PKA activation by 8Br-cAMP (10 μM) demonstrated that the kinase was significantly activated only after 30 minutes of exposure to the analog. In the bovine coronary artery, cAMP (10 - 100 μM) relaxed potassium-depolarized helical strips and significantly activated soluble PKA in a dose-dependent manner. dBu-cAMP (10 - 100 μM) affected neither tension nor soluble PKA activity. 8Br-cAMP (10 - 100 μM) did not affect the coronary artery tension but did activate soluble PKA. Both smooth muscle preparations were homogenized with charcoal prior to the determination of PKA activity in order to minimize artifactual assay results. As a further precaution, extracellularly associated cAMP and analogs were also washed from bovine coronary artery strips after the incubation period. These controls allowed for a valid assessment of PKA activity in the cyclic nucleotide-treated tissues. The results of the tension and kinase studies demonstrate a lack of correlation between activation of PKA and inhibition of rat vas deferens contraction or relaxation of bovine coronary artery. This does not support the hypothesis that the kinase is responsible for cAMP-induced relaxation of vascular and non-vascular smooth muscle. While the mechanism by which exogenous cAMP and specific analogs induce relaxation in some smooth muscle preparations remains unclear, it can be suggested that PKA activation is not necessarily required for the final functional effect. / Medicine, Faculty of / Anesthesiology, Pharmacology and Therapeutics, Department of / Graduate

published_or_final_version / Physiology / Master / Master of Philosophy

published_or_final_version / Pharmacology / Master / Master of Research in Medicine

No description available.

No description available.

No description available.